HGNC Approved Gene Symbol: RPL3
Cytogenetic location: 22q13.1 Genomic coordinates (GRCh38): 22:39,312,882-39,319,623 (from NCBI)
RPL3 is an essential and indispensable component for formation of the ribosomal peptidyltransferase center. It has a role in aminoacyl-tRNA binding, peptidyltransferase activity, drug resistance, translational frame maintenance, and virus replication. RPL3 also acts as a binding site for a ribosome inhibitory protein (Meskauskas and Dinman, 2007).
Adams et al. (1992) isolated the 3-prime region of an RPL3 cDNA as a human brain EST. The complete coding sequence of the human RPL3 gene has been deposited in GenBank (X73460). The deduced RPL3 protein has 403 amino acids.
Cuccurese et al. (2005) identified an RPL3 splice variant in a human lung carcinoma cell line that was induced by pharmacologic blockade of the nonsense-mediated mRNA decay pathway. This splice variant retains the 3-prime-most 180 nucleotides of intron 3, resulting in an in-frame premature termination codon. Northern blot analysis showed that the variant transcript is 1.5 kb, while the major RPL3 transcript is 1.3 kb. Intron 3 is highly conserved in human, mouse, and bovine RPL3.
Cuccurese et al. (2005) blocked nonsense-mediated mRNA decay using cycloheximide and wortmannin and observed pronounced accumulation of the 1.5-kb RPL3 splice variant, but no change in the level of the major RPL3 transcript. The level of the 1.5-kb transcript progressively decreased following drug withdrawal. RPL3 protein overexpression resulted in accumulation of the alternative transcript in a dose-dependent manner. Cuccurese et al. (2005) concluded that the RPL3 protein regulates alternative splicing of the RPL3 gene.
Meskauskas and Dinman (2007) stated that RPL3 has 2 long tentacle-like structures that extend deep into the mostly rRNA core of the ribosome. The central extension, called the 'W finger,' reaches all the way to the A-site side of the peptidyltransferase center. Meskauskas and Dinman (2007) used targeted mutagenesis and structural, biochemical, and genetic approaches to examine the W finger of S. cerevisiae Rpl3. The findings suggested a model in which RPL3 plays a role in synchronizing aminoacyl-tRNA accommodation and translocation by functioning as a sensor of tRNA occupancy at the A site of the peptidyltransferase center.
Duga et al. (2000) determined that the RPL3 gene contains 10 exons and spans about 6.7 kb. Introns 1, 3, 5, and 7 of the RPL3 gene encode the C/D box small nucleolar RNAs (snoRNAs) U43 (SNORD43; 611068), U86 (611069), U83A (SNORD83A; 611070), and U83B (SNORD83B; 611071), respectively. Intron 4 harbors a 283-bp Alu-SP-like repeat.
By somatic cell hybrid and radiation hybrid mapping analyses, Kenmochi et al. (1998) mapped the human RPL3 gene to 22q.
Duga et al. (2000) identified a polymorphic 19-bp deletion within intron 6 of the RPL3 gene that showed an allelic frequency of about 3% in a Northern Italian population.
Adams, M. D., Dubnick, M., Kerlavage, A. R., Moreno, R., Kelley, J. M., Utterback, T. R., Nagle, J. W., Fields, C., Venter, J. C. Sequence identification of 2,375 human brain genes. Nature 355: 632-634, 1992. Note: Comment: Nature 357: 367-368, 1992. [PubMed: 1538749] [Full Text: https://doi.org/10.1038/355632a0]
Cuccurese, M., Russo, G., Russo, A., Pietropaolo, C. Alternative splicing and nonsense-mediated mRNA decay regulate mammalian ribosomal gene expression. Nucleic Acids Res. 33: 5965-5977, 2005. [PubMed: 16254077] [Full Text: https://doi.org/10.1093/nar/gki905]
Duga, S., Asselta, R., Malcovati, M., Tenchini, M. L., Ronchi, S., Simonic, T. The intron-containing L3 ribosomal protein gene (RPL3): sequence analysis and identification of U43 and of two novel intronic small nucleolar RNAs. Biochim. Biophys. Acta 1490: 225-236, 2000. [PubMed: 10684968] [Full Text: https://doi.org/10.1016/s0167-4781(99)00237-7]
Kenmochi, N., Kawaguchi, T., Rozen, S., Davis, E., Goodman, N., Hudson, T. J., Tanaka, T., Page, D. C. A map of 75 human ribosomal protein genes. Genome Res. 8: 509-523, 1998. [PubMed: 9582194] [Full Text: https://doi.org/10.1101/gr.8.5.509]
Meskauskas, A., Dinman, J. D. Ribosomal protein L3: gatekeeper to the A site. Molec. Cell 25: 877-888, 2007. [PubMed: 17386264] [Full Text: https://doi.org/10.1016/j.molcel.2007.02.015]